A small population of vasculitogenic T cells expands and has skewed T cell receptor usage after culture with syngeneic smooth muscle cells |
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Authors: | Swanson Brad J Baiu Dana C Sandor Matyas Fabry Zsuzsa Hart Michael N |
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Affiliation: | Department of Pathology and Laboratory Medicine, 6152 MSC University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA. |
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Abstract: | Adoptive transfer of lymphocytes co-cultured with syngeneic smooth muscle (SM) cells to healthy recipient mice results in vasculitic lesions predominantly in post-capillary venules. The present study focuses on the mechanisms by which the disease-inducing CD4+T cells are generated in co-culture of lymphocytes with SM cells. Microvascular SM cells provide survival signals to both CD4+and CD8+naı̈ve syngeneic T cells and can activate only a limited range of CD4+T lymphocytes in culture. Additionally, approximately 0.4% of the original CD4+T cells divide at least twice in co-culture with SM cells. Survival of CD4+T cells in co-culture is dependent on a TCR mediated process, since transgenic CD4+cells with a unique specificity for a non-murine peptide do not survive in culture with SM. Analysis of TCR Vβ shows no superantigen activation of T cells following co-culture with SM cells. Spectratype analysis of TCR Vβ Jβ segment usage reveals a skewage in the TCR repertoire of T cells co-cultured with SM, and also of T cells from vasculitic lung. These results are consistent with a specific immune response of pathogenic T cells against one or more activating antigenic determinants of the microvascular SM cells, in contrast to non-specific cytokine activation. |
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